Proinflammatory cytokines in intestinal mucosa.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
A Raedler
Publications and source records attributed to A Raedler.
Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease.
Normal human lamina propria lymphocytes are in a heightened state of activation compared with peripheral blood with regard to cell-surface activation antigen expression (transferrin receptor, interleukin-2 receptor, 4F2) and the increased spontaneous secretion of immunoglobulins in vitro. This study evaluates the cell-surface expression of activation-associated antigens in different subpopulations of isolated colonic lamina propria mononuclear cells in inflammatory bowel disease. In pilot studies using three-color flow cytometry, autofluorescence was observed that was emitted by unstained lamina propria mononuclear cells, which interfered with both the sensitivity and the specificity of the analyses. Because a major portion of the intestinal lymphocyte populations of interest were autofluorescent, a method to remove autofluorescence signals was developed by designing a computer program for the subtraction of autofluorescence from the emissions of each individual cell. This technique increases both the sensitivity and specificity of flow-cytometric analyses of intestinal lamina propria mononuclear cells. Using fluorescence-activated cell-sorter analyses with subtraction of autofluorescence on a single-cell basis, increased expression of lymphocyte activation antigens (interleukin-2 receptor, transferrin receptor, 4F2) was found on the cell surface of isolated intestinal B cells, T cells, CD4+ T cells, and CD8+ T cells in both Crohn's disease and ulcerative colitis. Therefore, markedly increased intestinal lymphocyte activation is a major immunological alteration in inflammatory bowel disease and includes all lymphocyte subpopulations investigated in this study. In addition, 5-aminosalicylic acid, which is used for the treatment of intestinal inflammation in inflammatory bowel disease, inhibits the expression of cell-surface activation antigens on mitogen-activated peripheral blood lymphocytes in a dose-dependent manner. These observations suggest that lymphocyte activation may play an important role in underlying immune processes that lead to chronicity and perpetuation of inflammatory bowel disease and may implicate an additional mechanism for the therapeutic action of 5-aminosalicylic acid.
Aminosalicylic Acids↗
[Cytokines in intestinal mucosa].
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Acquired Immunodeficiency Syndrome↗
[Cytokines in chronic intestinal inflammation].
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Cytokines↗
[Color-coded Doppler sonography for phlebothrombosis].
Between November 1988 and February 1990, a total of 180 patients (76 men and 104 women; mean age 59 [17-79] years), suspected of having sustained a deep-vein or pelvic thrombosis were examined by colour Doppler ultrasound, the results being compared with those obtained by conventional phlebography. For 154 phlebographically confirmed acute venous thromboses (demonstrated by colour Doppler ultrasound in 153), four older thromboses (colour Doppler ultrasound: 7), and 22 without significant venous disease (colour Doppler ultrasound: 20), the specificity for colour Doppler ultrasound was 99%, its sensitivity 94%. In 49 patients with confirmed venous thrombosis thrombolytic treatment was started with 250,000 IU urokinase, followed by 62,500 IU hourly, the results being assessed by colour Doppler ultrasound and phlebography. This gave a specificity, compared with phlebography, of 99%, and a sensitivity of 97%. These data indicate that, in the diagnosis of venous thrombosis of the legs, colour Doppler ultrasound noninvasively provides information at least as reliable as phlebography. It may even be superior to phlebography in the demonstration of residual flow in partly thrombosed veins.
Adolescent↗
[Modification of gas exchange and metabolism by various hemodialysis procedures].
We compared the effects of various dialysate composition on pulmonary and transdialyzer gas exchange in patients during hemodialysis. Under acetate hemodialysis there was a permanent loss of CO2 (45-68 ml/min) into the dialysate resulting in a significant decrease of arterial pO2, which can be explained by a reduced alveolar ventilation. The pulmonary oxygen uptake increased up to +20% during treatment, reflecting rising energy metabolism and possibly increased cardiopulmonary instability. Using different concentrates for bicarbonatehemodialysis we saw a moderate to clinical relevant uptake of CO2 (40-60 ml/min) from the dialysate into the blood of the patients, cause the pCO2 in the dialysate varied between 45 and 115 mmHg. Bicarbonate hemodialysis with high pCO2-levels in the dialysate led to hyperventilation and markedly increased oxygen consumption. In critically ill hemodialysis patients the pathophysiologic effects on pulmonary gas exchange of either acetatehemodialysis and bicarbonatehemodialysis with high pCO2 can explain the higher incidence of severe complications.
Acetates↗
Changes of immunological parameters in healthy subjects under examination stress.
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Adult↗
[The role of arachidonic acid metabolism in the pathophysiology of chronic inflammatory intestinal diseases].
Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the bowel with unknown etiology. Alterations of intestinal and systemic immuno-regulation are probably of importance in the pathophysiology of both diseases. Moreover, recent studies suggest that polymorphonuclear granulocytes and probably macrophages are of particular importance in the initiation of an acute flare of the disease. Interest has therefore focused on arachidonic acid metabolites, in particular leukotrienes and prostaglandins, which are important mediators in granulocyte and macrophage activation and chemotaxis. The pathophysiologic importance of various leukotriene derivatives, particularly LTB4, has been well established whereas the actions of prostaglandins in vivo, in particular PGE2, are controversial. Numerous anti-inflammatory drugs such as glucocorticoids and salicylic acid derivatives have been successfully used to treat intestinal inflammation. One possible mechanism of action is the modulation of arachidonic acid metabolism and thus regulation of the genesis of active inflammatory mediators.
Anti-Inflammatory Agents↗
[Drug therapy of chronic inflammatory intestinal diseases].
The therapy of inflammatory bowel diseases (Crohn's disease, ulcerative colitis) has been improved in recent years. This is mainly due to our better understanding of application of aminosalicylates and steroids in regard to localization, activity, and type of chronic inflammatory bowel disease. Newly developed aminosalicylates like mesalazine provoke less side effects. Furthermore, they seem to be effective in the treatment of ileal inflammation of Crohn's disease. Therapy with immunosuppressive drugs like mercaptopurine, azathioprine, and cyclosporin A is justified in case of steroid-resistant Crohn's disease. Alternative therapeutic concepts are at present at the stage of clinical trial.
Aminosalicylic Acids↗
Assessment of in vivo activated T cells in patients with Crohn's disease.
Besides clinical indices, acute phase reactants and measurement of permeability of the gut immunological parameters have been proposed for assessment of clinical activity in Crohn's disease (CD). The latter refers in particular to the number of activated peripheral T cells (APT) which are found to be increased in patients with CD and ulcerative colitis. Further analysis of the subset of APT revealed that in CD their number is correlated to the histopathological ratings and the number of activated T cells of the affected mucosa. A major subset of APTs in CD and ulcerative colitis expresses receptors for IgA (Fc-alpha-R). This T cell subset seems to be characteristic of patients with inflammatory bowel diseases, exhibiting a specificity of 88% and a sensitivity of 92% for CD as compared with non-inflammatory bowel diseases. Methodological complexity turned out to be the major disadvantage of assessment of APT and their subsets.
Adolescent↗
[Comparative measurement of oxygen uptake and cardiac output at rest and during stress--evaluation of a new monitor for continuous determination of oxygen uptake and carbon dioxide release].
A new device for the continuous monitoring of oxygen uptake and carbon dioxide delivery is presented, which is based on a continuous expired gas analysis using a paramagnetic oxygen and an infrared-absorption carbon dioxide sensor. To validate the results, data of measured oxygen uptake and cardiac output calculated by the Fick principle were compared to synchronous thermodilution measurements at rest and during exercise. Measurements were performed at rest on 18 patients, additionally 13 of the patients were exercised with either 25 W or 50 W workload. The results indicate, for both measurement series, a significant correlation (r greater than 0.95, p less than 0.001) and exemplify that the measurement of oxygen uptake by expired gas analysis permits a precise analysis of the cardiovascular transport function during exercise.
Adult↗
Pathways mediating CRF-induced inhibition of gastric acid secretion in rats.
The pathways involved in mediating the central nervous system actions of corticotropin-releasing factor (CRF) on gastric acid secretion were examined in conscious rats. CRF (0.1-2.0 nmol) given cerebroventricularly inhibited gastric acid secretion stimulated by pentagastrin (P less than 0.01). This effect was abolished by cerebroventricular but not intravenous administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41). Ganglionic blockade with chlorisondamine chloride, noradrenergic blockade with bretylium, or adrenalectomy abolished the gastric inhibitory action of CRF whereas truncal vagotomy or opiate blockade with naloxone did not. A vasopressin receptor antagonist significantly inhibited but did not abolish the gastric inhibitory action of CRF. An intravenous infusion of epinephrine that mimicked the epinephrine plasma concentrations which were observed after cerebroventricular administration of CRF did not alter pentagastrin-stimulated gastric acid secretion. These results indicate that CRF acts within the central nervous system to inhibit gastric acid secretion by a specific receptor-mediated event. Inhibition of gastric acid secretion by CRF in conscious rats is mediated by efferent fibers of the sympathetic nervous system and in part by a vasopressin-dependent pathway but not by the parasympathetic nervous system, adrenal epinephrine release, or opiate-sensitive pathways.
Adrenalectomy↗
[Noninvasive monitoring of gas exchange: methodologic prerequisites and clinical use].
The noninvasive determination of the respiratory gas exchange (measurement of oxygen uptake and carbon dioxide delivery) permits the calculation of cardiac output by Fick principle and of the actual energy requirement of the patient (indirect calorimetry). A system is presented for the continuous measurement of oxygen uptake and carbon dioxide delivery, that bases on simple components, which are available on most intensive care units. The methodical problems are discussed and the improvement of the signal of the oxygen sensor by digital signal processing is described. Clinical measurements on 16 patients are presented, whose metabolic rate early after extracorporal circulation was measured. The results reveal, that 4.4 hours after ECC the metabolic rate is close to the calculated basic metabolic rate. They demonstrate the importance of indirect calorimetry as a future bedside monitoring routine.
Anesthesia, General↗
Immunology of ulcerative colitis.
Although much work has been done on the analysis of immunopathogenesis of UC, more mysteries remain to be solved in the future. One of the most interesting questions is (i) what initiates the immune response in the GALT of patients with UC. We are far from understanding whether inflammation starts from intrinsic or extrinsic factors. Valuable information has recently been assembled about (ii) antigen presentation and even more about (iii) regulation of immune response in the mucosa. Attractive models have been put forward concerning the integrity of GALT and in particular the role of Ig isotype and Ig subclasses. Further progress can be expected in particular from an analysis of homing of GALT-lymphocytes in disease. Thanks to improved methods, elucidation of regulation of immune response in patients with UC can be expected in the near future. This is less true for the effector functions of the immune response. In particular the action of mediators of acute and chronic inflammation, i.e. prostaglandins, leukotrienes and the broad spectrum of cytokines, represents a wide field of future research.
Colitis, Ulcerative↗
Activated Fc alpha T cells in Crohn's disease are involved in regulation of IgA.
Activated peripheral T cells (APT) of patients with Crohn's disease (CD) have been analysed for the expression of IgA-Fc receptors and for competence of IgA regulation. It was found that within the subset of APT an increased number of cells express binding sites for IgA (IgA-Fc), that was not found in other diseases with elevated numbers of APT. Moreover the number of IgA-Fc receptor expressing T cells was found to be increased in the inflamed mucosa too. Cocultures with autologous B cells revealed that isolated IgA-Fc receptor bearing T cells of patients with CD suppress IgA secretion. These data support the hypothesis that APT are involved in the immunopathogenesis of CD.
Antibodies, Monoclonal↗
Evidence for contrasuppression in patients with Crohn's disease.
Patients with Crohn's disease (CD) have elevated numbers of Vicia villosa agglutinin (VVA) binding cells in the peripheral blood. These cells represent a major subset of activated peripheral T cells. VVA binding T lymphocytes express either the T8 or the T4 determinant on their cell surface. In contrast in normal controls only a minor subset of peripheral T cell expresses binding sites for VVA. The majority of these cells coexpress T8. VVA binding T cells display no helper activity. Only in a subfraction of patients with CD and not in normal controls these cells mediate contrasuppressor activity for Ig and in particular for IgA. This subgroup of patients is characterized by the lack of extramucosal manifestations. It has now been shown that VVA binding T cells in their majority do not possess phenotypic features of helper inducer cells. This further supports the hypothesis of their involvement in contrasuppression. Moreover it was shown that IgA produced in the presence of VVA binding T cells is IgA1 and IgA2 (ratio 2:1) which are both modulated by VVA binding T cells.
Antigens, Differentiation, T-Lymphocyte↗
Central nervous system effects of corticotropin-releasing factor on gastrointestinal transit in the rat.
Corticotropin-releasing factor (CRF) administered into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit, but most markedly increased large bowel transit in a dose-related fashion in freely moving rats. Inhibition of gastric emptying induced by central administration of CRF was completely abolished by pretreatment of the animals with either the ganglionic blocking agent chlorisondamine or the opioid antagonist naloxone, or by noradrenergic blockade with bretylium, but not by truncal vagotomy. Either chlorisondamine, naloxone, or vagotomy--but not bretylium--reversed the inhibitory effect of central CRF on small bowel transit. Chlorisondamine or vagotomy, but neither bretylium nor naloxone, abolished the stimulatory effect of central CRF on large bowel transit. Neither hypophysectomy nor adrenalectomy altered the gastrointestinal motor responses induced by central administration of CRF. Intraperitoneal administration of CRF also significantly inhibited gastric emptying and stimulated large bowel transit but did not alter small bowel transit. These peripheral effects of CRF were not prevented by blockade of autonomic efferents with bretylium or chlorisondamine. It is concluded that (a) CRF acts within the central nervous system to delay gastric emptying, to inhibit small bowel transit, and to increase large bowel transit in freely moving rats and (b) CRF exerts these biological actions by modulation of the autonomic nervous system and, in part, by opioid pathways.
Animals↗
Stress-induced gastrointestinal secretory and motor responses in rats are mediated by endogenous corticotropin-releasing factor.
Corticotropin-releasing factor (CRF) has been implicated as a central nervous system mediator of stress. This study examined the effects of CRF and stress on gastric secretory and gastrointestinal motor functions in rats. Partial body restraint as a stress-producing stimulus significantly decreased gastric acid secretion, gastric emptying, and small bowel transit but markedly increased large bowel transit. Corticotropin-releasing factor given cerebroventricularly mimicked the gastrointestinal secretory and motor responses induced by partial body restraint. Cerebroventricular administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41), but not of the CRF fragment CRF-(1-20), prevented the gastrointestinal secretory and motor responses elicited either by partial body restraint or by exogenous administration of CRF in a dose-dependent fashion. These results suggest that the gastrointestinal secretory and motor responses in rats produced by stress (partial body restraint) are mediated by the endogenous release of CRF. They also indicate that CRF exerts its central nervous system actions on the gastrointestinal tract by a receptor-mediated event.
Animals↗